Reductive amination of nitriles using dihydrogen in the presence of a secondary amine is a known process for preparing tertiary amines from nitriles. These reductions are generally run at high temperatures and high hydrogen pressures, and often result in poor selectivity, low conversions, or high secondary amine loading. The preparation of dimethyl tertiary amines by the reduction of aliphatic nitriles with heterogeneous catalysts has been explored. These reactions generally use liquid (anhydrous) dimethylamine and are performed at high temperatures (at or above 120° C.) and high pressures (80-200 bar or 8-20 MPa). The catalysts for these reductions are usually either palladium on a support or Raney nickel.
Transfer hydrogenation is a well-known process for the reduction of unsaturated substrates that traces its roots to the classical Meerwein-Pondorf-Verley reduction. This process can avoid the hazards inherent in the use of hydrogen gas and the costs of operating at high pressure. Modern transfer hydrogenation generally utilizes a transition metal catalyst under mild conditions (temperatures below 100° C.) with a hydrogen donor molecule such as isopropanol, cyclohexene, cyclohexadiene, formic acid, formic acid salts, hydrazine, hydrazine salts, and amines. Transfer hydrogenation is most often used to reduce functionalities such as olefins, ketones, and nitro groups. Transfer hydrogenation of nitriles is known to selectively affording the corresponding primary amine as the major product, although proper choice of conditions can lead to the corresponding tertiary amine where the groups on nitrogen all derive from the nitrile. These reductions utilize either Raney nickel, palladium on carbon, or palladium clusters with a variety of hydrogen donors (isopropanol, ammonium formate, potassium formate, hydrazinium monoformate) in solvents varying from isopropanol (donor and solvent), methanol, ionic liquids, and aprotic solvents such as hexane or tetrahydrofuran. The reduction of a nitrile in the presence of a primary amine using Raney nickel catalyst has been reported. This reaction does not process via reductive amination but rather via disproportionation with the amine functioning as the hydrogen donor. Thus the reaction of a nitrile A and primary amine B under these conditions affords the alternative primary amine A and nitrile B. The reductive amination of nitriles with secondary amines using transfer hydrogenation to afford the corresponding tertiary amine has not been reported.